Cell cultures from the fetal mammalian central nervous system were used to study neuronal cell death associated with the envelope protein (gp120) from the Human Immunodeficiency Virus (HIV). Previous studies indicated that the purified IIIB isolate of HIV produced neuronal cell death in hippocampal cultures. Similar effects are now reported for purified native RFII and LAV isolates as well as for recombinant gp120 produced by vaccinia virus containing the LAV envelope encoding sequences. A recombinant gp160 from the IIIB encoding sequences expressed in insect cells with recombinant Baculovirus had no effect on neuronal survival. Two monoclonal antibodies against the mouse homologue (L3T4) of the T4 receptor were found to prevent neuronal cell death associated with gp120 in hippocampal neurons. Immunocyto-chemical evidence for the presence of L3T4 receptors on neurons in culture was discovered. The following peptide T sequences were shown to prevent gp120- induced neuronal cell death: TTSYT, TTNYT, NTSYG, SSTYR and ETWYS. Antiserum against ASTTTSYT was also found to prevent gp120-induced death, whereas pre-immune serum or serum from vehicle-injected animals were ineffective.